The chemical synthesis, mechanistic and biological evaluation of several clinically useful and/or biomedically important natural products is proposed. A mechanism of action for the recently introduced antibiotic bicyclomycin, is proposed. New synthetic methods are being developed to prepare bicyclomycin analogs that will be used to test these hypotheses. An interface of synthetic organic chemistry, mechanistic chemistry and protein (enzyme) chemistry will be used to conduct the bicyclomycin investigation. In addition, new synthetic methods to construct the [3.1.1] bicyclic acetal ring system of TXA2 using polymer-supported organometallic reagents will be studied. The chemical properties of this ring system will be eluciated in detail. Novel syntheses of C-nucleoside antibiotics such as showdomycin will be developed. Other synthetic programs related to Beta-lactam antibiotics such as thienamycin and antifungal antibiotics represented by the novel ansa piperazinomycin are being pursued.
| Silveira, Jay R; Raymond, Gregory J; Hughson, Andrew G et al. (2005) The most infectious prion protein particles. Nature 437:257-61 |
